In 1971 the National Cancer Act initiated a "War
on Cancer" that many sponsors predicted would cure cancer by
1976. Instead, this multibillion dollar research program has proven
to be a failure. The age-adjusted total cancer mortality rate climbed
steadily for decades until the early 1990s,35,36 when this
rate started to fall slowly, due largely to reduced smoking.37

In order to encourage continued support
for cancer research – now exceeding two billion dollars annually in
the U.S. alone – researchers and administrators have misled the public.
In 1987 the U.S. General Accounting Office (GAO) found that the statistics
of the National Cancer Institute (NCI) "artificially inflate
the amount of 'true' progress", concluding that even simple five-year
survival statistics were manipulated.38 For one thing,
the NCI termed five-year survival a "cure" even if the patient
died of the cancer after the five-year period. Also, by ignoring well
known statistical biases, the NCI falsely suggested advances had been
made in the therapy of certain cancers.38

Commenting on the research program's
discouraging results after 15 years, epidemiologist and program administrator
John C. Bailar III stated in 1986: "[We]
are losing the war against cancer. A shift in research emphasis, from
research on treatment to research on prevention, seems necessary if
substantial progress against cancer is to be forthcoming."39
In a review of cancer mortality more than a decade later, Bailar reiterated
in 1997: "The more promising areas are in cancer prevention."35

Why hasn't progress against cancer
been commensurate with the effort (and money) invested? One explanation
is the unwarranted preoccupation with animal research. Crucial genetic,40
molecular,41 immunologic42 and cellular43
differences between humans and other animals have prevented animal
models from serving as effective means by which to seek a cancer cure.
Mice are most commonly used, even though the industry’s own Lab Animal
magazine admits: "Mice are actually poor models of the
majority of human cancers."44 Leading
cancer researcher Robert Weinberg has commented: "The preclinical [animal] models of human cancer, in
large part, stink… Hundreds of millions of dollars are being wasted
every year by drug companies using these models."45 According to Clifton Leaf, a cancer survivor himself: "If you want to understand where the
War on Cancer has gone wrong, the mouse is a pretty good place to
start."45

2. AIDS

Despite their extensive use since the early 1980s,
animal models have not contributed significantly to AIDS research.
While mice, rabbits and monkeys born with severe combined immunodeficiency
can be infected with the AIDS virus (HIV), none develops the human
AIDS syndrome.46 Of over 150 chimpanzees infected with
HIV since 1984, only one allegedly developed symptoms resembling those
of AIDS.47,48 Even AIDS researchers acknowledge that chimpanzees,
as members of an endangered species who rarely develop an AIDS-like
syndrome, are unlikely to prove useful as animal models for understanding
the mechanism of infection or means of treatment.49

Other virus-induced immunodeficiency syndromes in
nonhuman animals have been touted as valuable models of AIDS, but
they differ markedly from AIDS in viral structure, disease symptoms
and disease progression.50 Animal experimenter Michael
Wyand, discussing anti-AIDS therapy, has acknowledged: “Candidate
antivirals have been screened using in vitro systems and those with
acceptable safety profiles have gone directly into humans with little
supportive efficacy data in any in vivo [animal] system. The reasons
for this are complex but certainly include … the persistent view held
by many that there is no predictive animal model for HIV infection
in humans.”51

AIDS researcher Margaret Johnston has concurred:
"HIV/AIDS [animal] models have not yielded a clear correlate
of immunity nor given consistent results on the potential efficacy
of various vaccine approaches."52 Indeed, since the
first HIV vaccine clinical trial in humans in 1987, more than 100
clinical trials have been funded by the U.S. National
Institute of Allergy and Infectious Diseases through mid-2006. Yet every one of the more than 50
preventive vaccines and more than 30 therapeutic vaccines that were
successful against HIV/AIDS in primate studies has failed in human
clinical trials.53

Human clinical investigation has isolated HIV, defined
the disease's natural course and identified risk factors.54
In vitro (cell and tissue culture) research using human white blood
cells has identified both the efficacy and toxicity of anti-AIDS medicines,
including AZT,55 3TC56 and protease inhibitors.57
Federal law, however, still mandates misleading and unreliable animal
toxicity testing.

3. Psychology and Drug Abuse

Animal "models" in experimental
psychology, which researchers traditionally subject to painful stimuli
in order to study their behavior, have been strongly criticized in
part because human psychological problems reflect familial, social
and cultural factors that cannot be modeled in nonhumans.58-63
Indeed, most psychologists disapprove of psychological animal experiments
which cause animal suffering.64

Harry Harlow's "maternal deprivation"
experiments in the 1950s and 1960s involved separating infant monkeys
from their mothers at birth and rearing them in total isolation or
with "surrogate" mothers made of wire and cloth. Their terror
and subsequent psychopathology, Harlow claimed, demonstrated the importance
of maternal contact. However, this had been shown conclusively in
previous human studies.65-68

Experimental psychology continues to
rely on painful research on animals, despite clinical psychologists'
disregard for animal research literature. A review of two clinical
psychology journals revealed that only 33 out of 4,425 citations (0.75%)
referred to animal-research studies.70

Animal models of alcohol and other
drug addictions are similarly ill-conceived, failing to reflect crucial
social, hereditary and mental factors. Pharmacologist Vincent Dole
has acknowledged: "Some 60 years of offering alcohol to animals
has produced no fundamental insights into the causes of this self-destructive
behavior or even a convincing analogue of pathological drinking."71

4. Genetic Diseases

Scientists have located the genetic defects of many
inherited diseases, including cystic fibrosis and familial breast
cancer. Trying to "model" these diseases in animals, researchers
widely use animals – mostly mice – with spontaneous or laboratory-induced
genetic defects. However, genetic diseases reflect interactions between
the defective gene and other genes and the environment. Consequently,
nearly all such models have failed to reproduce the essential features
of the analogous human conditions.72 For example, transgenic
mice carrying the same defective gene as people with cystic fibrosis
do not show the pancreatic blockages or lung infections that plague
humans with the disease,72 because mice and humans have
different metabolic pathways.73

B. Toxicity Tests

Numerous standard animal toxicity tests
have been widely criticized by clinicians and toxicologists. The lethal
dose 50 (LD50) test – which determines how much
of a drug, chemical or household product is needed to kill 50% of
a group of test animals – requires 60 to 100 animals (usually rats
and mice), most of whom endure great suffering. Because of difficulties
extrapolating the results to humans, the test is highly unreliable.74
Also, since such variables as an animal's age, sex, weight and strain
can have a substantial effect on the results, laboratories often obtain
widely disparate data with the same test substances.75,76
In vitro tests have been validated to replace the LD50 test,76-78 which was deleted
from the test guidelines of the Organisation for Economic Cooperation and Development (OECD) in 2002.79

The Draize eye irritancy test, in which
unanesthetized rabbits have irritant substances applied to their eyes,
yields results that are inherently unreliable in predicting human
toxicity.80 Humans and rabbits differ in the structure
of their eyelids and corneas, as well as in their ability to produce
tears. Indeed, when comparing rabbit to human data on duration of
eye inflammation after exposure to 14 household products, they differed
by a factor of 18 to 250.81 A battery of in vitro tests
would be less expensive and likely far more accurate than the Draize
test.75,82

Animal tests for cancer-causing substances,
generally involving rodents, are also notoriously unreliable. When
applied to human cancer causation, Lester Lave et al. found the false
positive rate of rodent testing to be as high as 95%.83
The authors stated: "Tests for human carcinogens
using lifetime rodent bioassays are expensive, time-consuming and
give uncertain results." The
tremendous economic costs of such research have recently been reported
in a study which examined over 500 rodent carcinogenicity studies
and concluded that rodent cancer assays are scientifically invalid
and fiscally indefensible.84

A combination of in vitro tests provides
data that compares favorably with existing carcinogenicity databases
and costs far less than animal tests.85 In the late 1980s,
the U.S. National Cancer Institute (NCI) developed a panel of 59 human
cancer cell lines to screen compounds for anti-cancer activity, due
to its "dissatisfaction with
the performance of prior in vivo primary screens [animal cancer assays]."86 This panel replaced animal testing
at the NCI in 1990, by which time the agency had also adopted a panel
of about 100 human cell lines to screen compounds for carcinogenicity.87

Animal tests for teratogens (drugs and chemicals
that cause birth defects) are equally misleading and unreliable. Jarrod
Bailey et al. conducted a comprehensive review of animal tests of
1,396 different substances and found that of those substances known
to cause birth defects in humans, animal tests indicated that almost
half were safe. Conversely, of those substances known to be safe in
humans, animal tests indicated that almost half were dangerous. And
almost one-third of all substances tested yielded varying results,
depending on the species used.88 In pregnant animals, differences in the physiological structure, function
and biochemistry of the placenta aggravate the usual differences in
the absorption, distribution, metabolism and excretion of drugs and
chemicals that exist between species, thus making reliable predictions
in pregnant women impossible.88

In vitro tests, such as the embryonic stem-cell test, the whole embryo culture,
and the micromass test, provide data that are considerably more reliable
and predictive and far less costly than animal teratogenicity tests.
While such in vitro tests currently utilize cells and embryos derived
from animals (thus rendering their extrapolation to humans difficult),
advances in human cell culture technology should, in the future, permit
a much closer in vitro approximation of teratogenesis in humans.88

C. Medical Education

Animal laboratories are not necessary for teaching
biological and medical principles and skills to medical students,
and 85% of U.S. and Canadian medical schools have eliminated animal
labs from their educational curricula.89 Effective alternative
teaching methods include lectures and written course materials, videos
and interactive virtual reality programs, mentored patient care encounters
and surgery participation, and lifelike programmable interactive patient
simulators. Comparative studies of simulation technologies for many
aspects of medical education (e.g. anatomy, physiology, pharmacology,
surgical skills, trauma management and invasive procedures) have repeatedly
demonstrated superior training outcomes, fewer patient complications,
greater trainee acceptance, and more efficient use of educational
time and resources.90-99

Further evidence of the emerging primacy of simulation-based
medical education is the American College of Surgeons’ (ACS) endorsement
and implementation of the TraumaMan® simulator to replace the use of
animals and human cadavers for its Advanced Trauma Life Support (ATLS)
program. Furthermore, in 2006 the ACS implemented a sweeping educational
reform that incorporated a wide variety of simulators to eliminate
animal use in its own conferences and educational programs, in addition
to establishing the Accredited Education Institutes program to achieve
the same goal in surgery training programs.100

Scientific Limitations of Animal Models

Animal studies can neither confirm nor refute hypotheses
about human physiology or pathology; human clinical investigation
is the only way such hypotheses can be tested. At best, animal experiments
can suggest new hypotheses that might be relevant to humans.101,102
However, there are countless other, far superior ways to derive new
hypotheses.2,101

How valuable is animal experimentation? The Medical
Research Modernization Committee's review of ten randomly chosen animal
models of human diseases did not reveal any important contributions
to human health.103 Although the artificially induced conditions
in animals were given names analogous to the human diseases they were
intended to simulate, they differed substantially from their human
"counterparts" in both cause and clinical course. Also,
the study found that treatments effective in animals tended to have
poor efficacy or excessive side effects in human patients.103
Indeed, when MRMC physicians evaluate specific animal-research projects,
they consistently find them to be of little, if any, relevance to
the understanding or treatment of human diseases.104-110

MRMC's reviews have revealed that, because animal
models differ from human diseases, researchers tend to investigate
those aspects of the animal's condition that resemble features of
the human disease, generally ignoring or discounting fundamental anatomical,
physiological and pathological differences. Because most disease
processes have system-wide effects and involve many interacting factors,
focusing on only one aspect of a disease belies the actual complexity
of biological organisms.

For example, artifact from unnaturally induced strokes
in animals has repeatedly misled researchers.117,120 Macleod
et al. reported on over 4,000 studies demonstrating efficacy for more
than 700 drugs in animal models of stroke.121 About 150
drugs subsequently tested in human clinical trials failed to show
any benefit.122 Only recombinant human tissue plasminogen
activator (rt-PA) administered within three hours of stroke onset
has proven beneficial in reducing symptoms, but it was associated
with ten times as many intracerebral hemorrhages and did not increase
survival.123 David Wiebers et al. have concluded: "Ultimately, the answers to many of
our questions regarding the underlying pathophysiology and treatment
of stroke do not lie with continued attempts to model the human situation
more perfectly in animals, but rather with the development of techniques
to enable the study of more basic metabolism, pathophysiology and
anatomical imaging detail in living humans."117

Since 1990, several hundred gene therapies that were
successful in animal studies have been tested on thousands of patients
worldwide. Yet only one gene therapy, for children with the severe
immune system disorder X-SCID, appears to have succeeded. Of the ten
successfully treated children, however, three developed leukemia and
one of them died of it – a side effect that animal experiments failed
to predict and that prompted the U.S. Food and Drug Administration
(FDA) to halt several gene therapy trials in 2005.124,125 Similarly,
a highly touted gene therapy that cured dogs of hemophilia was discontinued
in 2004 due to "afety problems … in the human trial that weren’t predicted
in animal studies",including liver damage.126,127

Animal tests are frequently misleading.128
Milrinone increased survival of rats with artificially induced heart
failure, but humans taking this drug experienced a 30% increase in
mortality.129 Fialuridine appeared safe in animal tests,
but it caused liver failure in 7 out of 15 humans taking the drug,
five of whom died and two of whom required a liver transplantation.130
Animal studies failed to predict the dangerous heart valve abnormalities
in humans caused by the diet drugs fenfluramine and dexfenfluramine.131

Hormone replacement therapy increased
women’s risk of heart disease, breast cancer and stroke, but experiments
with mice, rabbits, pigs and monkeys had predicted the opposite effect.132
The widely prescribed arthritis painkiller Vioxx appeared safe and
even beneficial to the heart in animal tests, but was withdrawn from
the global market in 2004 after causing an estimated 320,000 heart
attacks, strokes and cases of heart failure worldwide – 140,000 of
them fatal.133David Graham, the
Associate
Director for Science and Medicine in the Office of Drug Safety at
the FDA, described Vioxx as
the "single greatest drug safety catastrophe in the history of
this country or the history of the world".134 Animal tests also failed to predict
the cases of partial or total blindness suffered by some men taking
the popular impotence drug Viagra.135,136 Despite mandatory,
extensive animal testing, adverse drug reactions remain the fifth
leading cause of mortality in the United States, accounting for more
than 100,000 deaths per year.137

In London in March 2006, a new anti-inflammatory
drug called TGN1412 caused devastating reactions including multiple
organ failure in all six volunteers in phase 1 clinical trials, despite "proof
of safety" established by tests on monkeys who
were given 500 times the human dose. Many commentators noted that
the animal tests provided a false sense of security. The incident
prompted calls for an overhaul of drug safety testing requirements
and clinical trial design.138

In animal tests to evaluate the carcinogenicity of
the artificial sweetener saccharin, the weight-adjusted daily saccharin
dose given to rats was equivalent to a human consuming about 1,100
cans of soda containing saccharin. Such massive dosing alone can result
in cancers, regardless of a compound's actual carcinogenicity at typical
human exposure levels.116 Extrapolating such data to humans
is further complicated by the observation that saccharin-induced bladder
cancers occurred only in male rats. It was later found that male rats
possess a protein in greater quantity than female rats (and lacking
in humans) that interacted with saccharin to form irritating crystals
in the male rats' bladders, causing cancer. The fact that some rats
developed cancers did not (and cannot) clarify whether or not saccharin
causes cancer in humans.139

Similarly, despite almost 40 years of human consumption,
its use in more than 9,000 food and beverage products worldwide, and
the irrelevance of animal tests to humans, the artificial sweetener
aspartame is still being tested on animals, and regulatory authorities
continue to evaluate the results of such studies. Most recently, an
Italian study carried out in 2005 on 1,800 rats demonstrated an increased
risk for lymphomas and leukemias in rats fed aspartame – but only
in females.140 A subsequent NCI epidemiological study involving
340,045 men and 226,945 women and reported on at the 2006 meeting
of the American Association for Cancer Research refuted the findings
in rats.141 So, despite male rats getting bladder cancers
from saccharin and female rats getting lymphomas and leukemias from
aspartame, no cancer risk from either sweetener has been found for
humans of either sex.

Scientists recognize that, even between humans, gender,
ethnicity, age and health can profoundly influence drug effects.142,143
Perhaps the most striking example of the specificity of drug effects
comes from the demonstration that even human monozygotic twins display
different drug responses and that these become more disparate as the
twins age.144 Obviously, extrapolating data between species
is much more hazardous than within a species. Indeed, according to
the FDA, a staggering 92% of all drugs found safe and therapeutically
effective in animal tests fail during human clinical trials due to
their toxicity and/or inefficacy, and are therefore not approved.145-147
Furthermore, over half of the mere 8% of drugs which do gain FDA approval
must later be withdrawn or relabeled due to severe, unexpected side
effects.148

Risks of Animal Experimentation

In addition to squandering scarce resources and providing
misleading results, animal experimentation poses real risks to humans.
The mind-set that scientific knowledge justifies and requires harming
innocent individuals endangers all who are vulnerable. Even after
Nazi and Japanese experiments on prisoners horrified the world, American
researchers denied African-American men syphilis treatment in order
to assess the disease's natural progression,149 they deliberately
exposed students and minorities to toxic chemicals in order to determine
safe levels of exposure to pesticides,150 they
intentionally exposed thousands of unsuspecting civilians
to lethal bacteria in order to test biological warfare,151
they injected cancer cells into nursing home patients,149
subjected unwitting patients to dangerous radiation experiments,152
and, despite no chance of success, transplanted nonhuman primate and
pig organs into children, as well as chronically ill and impoverished
people.153 Psychiatrist Robert Jay Lifton argues that this
"science at any cost" mentality may have provided medical
justification for the Holocaust.154

Furthermore, through animal research, humans have
been exposed to a wide variety of deadly nonhuman primate viruses.
About 16 laboratory workers have been killed by the Marburg virus
and other monkey viruses, and two outbreaks of Ebola have occurred
in American monkey colonies.155-157 Polio vaccines grown
on monkey kidney cells exposed millions of Americans to the simian
virus 40, which causes human cells to undergo malignant transformation
in vitro and has been found in several human cancers.158
Ignoring the obvious public health hazards, researchers transplanted
baboon bone marrow cells into an AIDS patient. The experiment was
unsuccessful;159 moreover, a large number of baboon viruses,
which the patient could have spread to other people, may have accompanied
the bone marrow. Indeed, animal experimentation may have started the
AIDS epidemic. HIV-1, the principal AIDS virus, differs markedly from
all other viruses found in nature, and there is evidence that it originated
either through polio vaccine production using monkey tissues160,161
or through manufacture in American laboratories, where HIV-like viruses
were being produced by cancer and biological weapons researchers in
the early 1970s.162

Failing to learn from the AIDS epidemic, many policy
makers and industrial interest groups support animal-to-human organ
transplants (from pigs and primates) known as xenotransplants. These
have failed in the past and will most likely continue to fail because
of tissue rejection, the impossibility of testing animal tissues for
unknown pathogens, and the prohibitive expense.163-165

Similarly, the rapidly expanding field of genetic
engineering includes adding genetic material to animals’ cells to
change the animals’ growth patterns or induce the animals to produce
human proteins in their milk, meat or urine. Harvesting such proteins
poses serious human health risks, such as exposure to pathogens (viruses,
prions and other microorganisms)166,167 or the development
of malignancies,168,169 allergic reactions170
or antibiotic resistance.171 These concerns contributed
to the European Union’s ban on rBGH, a genetically engineered bovine
growth hormone that increases cows’ milk production.172

The Importance of Clinical Research

Typically, medical discovery begins with a clinical
observation,9,10 which animal experimenters then try to
mimic with artificially induced conditions in laboratory animals.7
These researchers tend to highlight animal data that agrees with the
previous clinical finding, while discounting or ignoring conflicting
animal data (which is usually voluminous). Although animal experimentation
advocates routinely take credit for discoveries that actually occurred
in a clinical context,7 many clinicians have recognized
the primary role of human-based clinical research. Reviewing the history
of hepatitis, physician Paul Beeson concluded: “Progress in the understanding
and management of human disease must begin, and end, with studies
of man… Hepatitis, although an almost 'pure' example of progress by
the study of man, is by no means unusual; in fact, it is more nearly
the rule. To cite other examples: appendicitis, rheumatic fever, typhoid
fever, ulcerative colitis and hyperparathyroidism.”11

Similarly, key discoveries in immunology,12
anesthesiology,13 first aid,173 alcoholism71,174
and psychopharmacology175,176 were based primarily on human
clinical research and investigation. Furthermore, clinical research
is the only means by which effective public health education and prevention
programs can be developed and evaluated.